A new study reveals that astrocytes—star-shaped support cells traditionally viewed as passive partners of neurons—play a previously underappreciated role in the maturation of coordinated movement. A research team led by Director C. Justin LEE and Senior Research Fellow HONG Sungho of the Center for Memory and Glioscience within the Institute for Basic Science (IBS), in collaboration with Professor Erik DE SCHUTTER from the Compational Neuroscience Unit at the Okinawa Institute of Science and Technology (OIST), Japan, has uncovered how astrocytes regulate inhibitory signaling in the cerebellum during development, enabling the emergence of flexible and precise motor coordination.

Motor coordination allows animals and humans to combine movements of different body parts in a flexible manner, especially when navigating complex or changing environments. Although this ability continues to improve throughout development and typically reaches its peak in adulthood, the neural circuits responsible for coordination—particularly those in the cerebellum—are thought to reach structural maturity relatively early in life. This discrepancy has long raised an unresolved question: why does motor coordination continue to improve after cerebellar circuits appear fully developed?

To investigate this puzzle, the researchers examined cerebellar granule cells, which represent one of the most abundant neuron populations in the brain. These cells are regulated by tonic inhibition, a persistent “always-on” form of inhibitory signaling mediated by the neurotransmitter GABA. Unlike transient synaptic inhibition, tonic inhibition provides a continuous regulatory background that stabilizes neuronal excitability and supports reliable information processing.

Using electrophysiological recordings, the team measured tonic inhibitory currents in granule cells from young mice (3-4 weeks old) and adult mice (8-12 weeks old). Surprisingly, the overall strength of tonic inhibition remained largely unchanged between the two age groups. However, a closer analysis revealed a major shift in the source of the inhibitory signal.

In younger animals, tonic inhibition was primarily generated by GABA released from inhibitory neurons, which diffuses beyond synaptic sites and accumulates in the surrounding extracellular space. In contrast, in adult animals the dominant source of tonic inhibition became astrocyte-derived GABA, released through Bestrophin-1 (Best1) channels.

Further experiments showed that this transition is closely associated with changes in GABA transport dynamics. In adult mice, the activity of GABA transporters (GATs)—proteins responsible for removing GABA from the extracellular space—increases substantially. This enhanced clearance reduces the effectiveness of neuron-derived spillover GABA, thereby shifting the balance toward astrocytes, which continuously supply GABA independently of synaptic activity.

To explore how this cellular transition influences information processing at the circuit level, the researchers constructed a large-scale computational model of the cerebellar neural network comprising approximately one million neurons, incorporating physiological data from their experiments. Professor De Schutter explains: “Our simulations indicated that when tonic inhibition becomes increasingly astrocyte-driven, interactions between granule cell populations responding to different inputs become weaker. As a result, individual granule cell groups are able to process incoming signals more independently.”

Senior Research Fellow HONG Sungho, whose work on the topic began at OIST, adds: “This shift in network dynamics could provide a neural mechanism for more flexible motor coordination. As different groups of neurons representing movements of separate body parts interfere less with each other, the brain can more easily combine multiple movement strategies—such as switching between hopping, walking, or turning—to accomplish the same behavioral goal.”

The researchers then tested these predictions experimentally using a deep learning-based behavioral analysis system capable of reconstructing mouse posture in three dimensions during spontaneous movement. Adult mice exhibited a wider variety of limb coordination patterns compared with younger animals. However, this increased diversity of movement was absent in adult mice lacking the Best1 gene, which disrupts astrocyte-mediated tonic inhibition.

Detailed analysis revealed that both young mice and adult Best1-knockout mice showed more tightly coupled limb movements, indicating reduced independence between different body parts during locomotion. These findings confirm that astrocyte-driven tonic inhibition is a critical factor in the late-stage maturation of flexible motor coordination.

Director C. Justin LEE said, “This study expands the conventional neuron-centric understanding of brain development to encompass the perspective of neuron-astrocyte interactions,” and added, “A deeper understanding of astrocyte function could inform not only research into developmental and degenerative motor disorders, but also the design of movement control systems for robotics and physical AI inspired by brain principles.”

The study was published online on February 18, 2026, in Experimental & Molecular Medicine.